Microdialysis is an extremely versatile technique for sampling from blood and tissues in living animals and humans. A small probe, similar to a very thin intravenous needle (approximately one-half millimeter diameter) is inserted via needle stick. The probe has porous walls and an internal buffer flowing through it. Molecules enter the probe by diffusion and then are carried out to be measured.
Microdialysis has many appealing features, including that it is minimally invasive and remarkably versatile. It has been a valuable research tool in studying neurotransmitters in the brain, performing studies of drug distribution in tissues and blood, and many other purposes. Nevertheless, microdialysis has remained predominantly a research tool for over two decades because there are several problematic issues intrinsic to microdialysis systems that prevent it from becoming a robust clinical tool. One issue is that microdialysis probes are prone to fouling (or biofouling), which is a process that starts immediately upon contact of a synthetic material with the body, when cells, proteins, blood clots and other biological components adhere to the surface of the foreign material. Fouling remains a problem for any separation medium since it can significantly reduce acquisition of biomolecules, such as glucose. Within tissue other processes such as scar formation and cellular attack also slowly degrade the access of sensors to the surrounding interstitial fluid.
Another issue with microdialysis involves the undesirable phenomenon of water transport across the membrane by ultrafiltration (differential hydrostatic pressure) and osmosis (which is diffusion-based movement of water molecules). Ultrafiltration into the probe will augment analyte recovery while ultrafiltration out of the probe will reduce recovery. Both increase variability. The larger pore membranes used to capture macromolecules, such as proteins and nucleic acids, are particularly prone to ultrafiltration/osmosis. Ultrafiltration/osmosis during microdialysis is currently not measured in a real-time fashion.
Another issue is that the recovery of molecules via microdialysis, their transport through the system and their analysis by on-board detectors, is affected by flow rate. The slower the flow rate, the higher the recovery of analyte molecules from the surrounding medium since more time is allowed for transport across the membrane. Although many have experimented with different flow rates, there is no “intelligent” control circuit to optimize flow rates in microdialysis systems.
Because of these complications, microdialysis systems can fail or give unreliable data. Consequently, although some have used microdialysis for studies in the injured human brain, and for continuously monitoring glucose in the blood, clinical devices that take advantage of microdialysis have not evolved.